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Nat Neurosci. 2006 Oct;9(10):1231-3. Epub 2006 Sep 17.

Kinase activity of mutant LRRK2 mediates neuronal toxicity.

Author information

1
Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA. wsmith60@jhmi.edu

Abstract

Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson disease and some cases of sporadic Parkinson disease. Here we found that LRRK2 kinase activity was regulated by GTP via the intrinsic GTPase Roc domain, and alterations of LRRK2 protein that reduced kinase activity of mutant LRRK2 correspondingly reduced neuronal toxicity. These data elucidate the pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms of sporadic Parkinson disease and suggest therapeutic targets.

PMID:
16980962
DOI:
10.1038/nn1776
[Indexed for MEDLINE]

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